[HTML][HTML] B cell zone reticular cell microenvironments shape CXCL13 gradient formation

J Cosgrove, M Novkovic, S Albrecht, NB Pikor… - Nature …, 2020 - nature.com
J Cosgrove, M Novkovic, S Albrecht, NB Pikor, Z Zhou, L Onder, U Mörbe, J Cupovic
Nature communications, 2020nature.com
Through the formation of concentration gradients, morphogens drive graded responses to
extracellular signals, thereby fine-tuning cell behaviors in complex tissues. Here we show
that the chemokine CXCL13 forms both soluble and immobilized gradients. Specifically,
CXCL13+ follicular reticular cells form a small-world network of guidance structures, with
computer simulations and optimization analysis predicting that immobilized gradients
created by this network promote B cell trafficking. Consistent with this prediction, imaging …
Abstract
Through the formation of concentration gradients, morphogens drive graded responses to extracellular signals, thereby fine-tuning cell behaviors in complex tissues. Here we show that the chemokine CXCL13 forms both soluble and immobilized gradients. Specifically, CXCL13+ follicular reticular cells form a small-world network of guidance structures, with computer simulations and optimization analysis predicting that immobilized gradients created by this network promote B cell trafficking. Consistent with this prediction, imaging analysis show that CXCL13 binds to extracellular matrix components in situ, constraining its diffusion. CXCL13 solubilization requires the protease cathepsin B that cleaves CXCL13 into a stable product. Mice lacking cathepsin B display aberrant follicular architecture, a phenotype associated with effective B cell homing to but not within lymph nodes. Our data thus suggest that reticular cells of the B cell zone generate microenvironments that shape both immobilized and soluble CXCL13 gradients.
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